Illicit Drugs

Overview – Illicit Drugs

Illicit drugs are psychoactive substances used non-medically for their mood-altering effects, and they pose serious health, social, and economic risks. Understanding the pharmacodynamics, clinical effects, and complications of illicit drugs is crucial for final-year medical students. These substances primarily act on neurotransmitter systems such as dopamine, serotonin, and gamma-aminobutyric acid (GABA), often hijacking the brain’s mesolimbic dopamine pathway, which reinforces reward and pleasure. This page provides a high-yield breakdown of major illicit drugs by substance class and mechanism.

Benzodiazepines

Pharmacodynamics

• GABA-A receptor modulators
• ↑ GABA-A channel affinity → ↑ Cl⁻ influx → hyperpolarisation → CNS inhibition

Clinical Effects

Immediate:

• Anxiolysis, sedation, muscle relaxation
• Respiratory depression (especially when combined with alcohol or opioids)

Chronic:

• Tolerance and dependence
• Withdrawal: tremor, anxiety, seizures (can be life-threatening)

Opioids (Heroin, Codeine, Fentanyl)

Pharmacodynamics

• μ and δ opioid receptor agonists
• Inhibit GABA release in nucleus accumbens → disinhibition of dopamine neurons → ↑ dopamine release
• Stimulates mesolimbic pathway

Note: Heroin is more lipophilic than morphine → faster BBB penetration → stronger euphoria

Clinical Effects

Immediate:

• Euphoria, analgesia, pinpoint pupils, sedation
• Nausea/vomiting, hypothermia, respiratory depression

Chronic:

• Collapsed veins, skin abscesses, infections (HIV, hepatitis), chronic constipation
• Fertility issues, malnutrition, overdose risk, significant social consequences

Cocaine

Pharmacodynamics

• Blocks reuptake of dopamine, serotonin, noradrenaline → ↑ synaptic levels
• Strongly stimulates mesolimbic pathway

Clinical Effects

Immediate:

• Tachycardia, hypertension, hyperthermia, mydriasis, euphoria, ↑ energy
• ↑ risk-taking behaviour, agitation, paranoia, hallucinations

Toxicity:

• Chest pain, MI, seizures, psychosis, sudden death

Chronic:

• Nasal septum perforation, insomnia, depression, needle-related infections

Amphetamines (Including Speed and Ice)

Pharmacodynamics

• Reverses dopamine reuptake transporter → dopamine released into synapse
• Inhibits vesicular packaging of dopamine → amplifies synaptic dopamine
• Stimulates mesolimbic dopamine pathway

Note:

• “Ice” = crystal methamphetamine, ~80% purity
• “Speed” = powdered, ~20–30% purity

Clinical Effects

Immediate:

• Euphoria, hypervigilance, insomnia, tachycardia, hypertension
• Paranoia, hallucinations, compulsive scratching, increased libido

Amphetamine Psychosis:

• Delusions, aggression, bizarre behaviour

Chronic:

• Malnutrition, “meth mouth,” depression, anxiety, cognitive impairment
• Hypertension-related complications

Ecstasy (MDMA)

Pharmacodynamics

• Inhibits vesicular monoamine transporter
• ↑ Serotonin, dopamine, noradrenaline in cytoplasm
• Reverses reuptake transporters → flood of monoamines in synapse

Clinical Effects

Immediate (lasting up to 6 hours):

• Euphoria, heightened empathy, jaw clenching, hyperthermia, dehydration
• Seizures, vomiting, hallucinations

Long-Term:

• Insomnia, bruxism (teeth grinding), mood disturbances, poor concentration

Overdose/Adverse Reaction:

• Hypertensive crisis, atrial fibrillation, hyperthermia → death

Pathophysiology – Mesolimbic Dopamine Pathway

Nearly all addictive drugs hijack the mesolimbic dopamine system, particularly involving the ventral tegmental area (VTA) and nucleus accumbens. This reward circuitry, which is meant to reinforce survival behaviours, is overstimulated by drugs, leading to reinforcement of drug-seeking and compulsive use. Chronic activation leads to structural and functional changes underpinning tolerance, dependence, and withdrawal.

Summary – Illicit Drugs

Illicit drugs such as opioids, amphetamines, ecstasy, cocaine, alcohol, and benzodiazepines each produce characteristic physiological and psychological effects, with addiction rooted in overactivation of the mesolimbic dopamine pathway. These substances carry high risks of harm, dependence, and withdrawal, making their understanding essential in clinical practice. For a broader context, see our Psychiatry & Mental Health Overview page.